tbuckley/cabot-search huggingface dataset:
Waning of vaccine effectiveness against moderate and severe covid-19 among adults in the US from the VISION network: test negative, case-control study
Authors: Jill M Ferdinands, Suchitra Rao, Brian E Dixon, Patrick K Mitchell, Malini B DeSilva, Stephanie A Irving, Ned Lewis, Karthik Natarajan, Edward Stenehjem, Shaun J Grannis, Jungmi Han, Charlene McEvoy, Toan C Ong, Allison L Naleway, Sarah E Reese, Peter J Embi, Kristin Dascomb, Nicola P Klein, Eric P Griggs, I-Chia Liao, Duck-Hye Yang, William F Fadel, Nancy Grisel, Kristin Goddard, Palak Patel, Kempapura Murthy, Rebecca Birch, Nimish R Valvi, Julie Arndorfer, Ousseny Zerbo, Monica Dickerson, Chandni Raiyani, Jeremiah Williams, Catherine H Bozio, Lenee Blanton, Ruth Link-Gelles, Michelle A Barron, Manjusha Gaglani, Mark G Thompson, Bruce Fireman
Journal: BMJ (2022)

To estimate the effectiveness of mRNA vaccines against moderate and severe covid-19 in adults by time since second, third, or fourth doses, and by age and immunocompromised status.Test negative case-control study.Hospitals, emergency departments, and urgent care clinics in 10 US states, 17 January 2021 to 12 July 2022.893 461 adults (≥18 years) admitted to one of 261 hospitals or to one of 272 emergency department or 119 urgent care centers for covid-like illness tested for SARS-CoV-2.The main outcome was waning of vaccine effectiveness with BNT162b2 (Pfizer-BioNTech) or mRNA-1273 (Moderna) vaccine during the omicron and delta periods, and the period before delta was dominant using logistic regression conditioned on calendar week and geographic area while adjusting for age, race, ethnicity, local virus circulation, immunocompromised status, and likelihood of being vaccinated.45 903 people admitted to hospital with covid-19 (cases) were compared with 213 103 people with covid-like illness who tested negative for SARS-CoV-2 (controls), and 103 287 people admitted to emergency department or urgent care with covid-19 (cases) were compared with 531 168 people with covid-like illness who tested negative for SARS-CoV-2. In the omicron period, vaccine effectiveness against covid-19 requiring admission to hospital was 89% (95% confidence interval 88% to 90%) within two months after dose 3 but waned to 66% (63% to 68%) by four to five months. Vaccine effectiveness of three doses against emergency department or urgent care visits was 83% (82% to 84%) initially but waned to 46% (44% to 49%) by four to five months. Waning was evident in all subgroups, including young adults and individuals who were not immunocompromised; although waning was morein people who were immunocompromised. Vaccine effectiveness increased among most groups after a fourth dose in whom this booster was recommended.Effectiveness of mRNA vaccines against moderate and severe covid-19 waned with time after vaccination. The findings support recommendations for a booster dose after a primary series and consideration of additional booster doses.
Local TLR4 stimulation augments in situ vaccination induced via local radiation and anti-CTLA-4 checkpoint blockade through induction of CD8 T-cell independent Th1 polarization
Authors: Justin C Jagodinsky, Amber M Bates, Paul A Clark, Raghava N Sriramaneni, Thomas C Havighurst, Ishan Chakravarty, Erin J Nystuen, KyungMann Kim, Paul M Sondel, Won Jong Jin, Zachary S Morris
Journal: Journal for ImmunoTherapy of Cancer (2022)

Background Radiation therapy (RT) has been demonstrated to generate an in situ vaccination (ISV) effect in murine models and in patients with cancer; however, this has not routinely translated into enhanced clinical response to immune checkpoint inhibition (ICI). We investigated whether the commonly used vaccine adjuvant, monophosphoryl lipid A (MPL) could augment the ISV regimen consisting of combination RT and ICI. Materials/methods We used syngeneic murine models of melanoma (B78) and prostate cancer (Myc-CaP). Tumor-bearing mice received either RT (12 Gy, day 1), RT+anti-CTLA-4 (C4, day 3, 6, 9), MPL (20 µg IT injection days 5, 7, 9), RT+C4+MPL, or PBS control. To evaluate the effect of MPL on the irradiated tumor microenvironment, primary tumor with tumor draining lymph nodes were harvested for immune cell infiltration analysis and cytokine profiling, and serum was collected for analysis of antitumor antibody populations. Results Combination RT+C4+MPL significantly reduced tumor growth, increased survival and complete response rate compared with RT+C4 in both B78 and Myc-CaP models. MPL favorably reprogrammed the irradiated tumor-immune microenvironment toward M1 macrophage and Th1 TBET + CD4 + T cell polarization. Furthermore, MPL significantly increased intratumoral expression of several Th1-associated and M1-associated proinflammatory cytokines. In co-culture models, MPL-stimulated macrophages directly activated CD8 T cells and polarized CD4 cells toward Th1 phenotype. MPL treatment significantly increased production of Th1-associated, IgG2c antitumor antibodies, which were required for and predictive of antitumor response to RT+C4+MPL, and enabled macrophage-mediated antibody-dependent direct tumor cell killing by MPL-stimulated macrophages. Macrophage-mediated tumor cell killing was dependent on FcγR expression. In metastatic models, RT and MPL generated a systemic antitumor immune response that augmented response to ICIs. This was dependent on macrophages and CD4 + but not CD8+T cells. Conclusions We report the potential for MPL to augment the ISV effect of combination RT+C4 through FcγR, macrophage, and TBET + CD4 + Th1 cell dependent mechanisms. To our knowledge, this is the first report describing generation of a CD8 + T cell-independent, Th1 polarized, systemic antitumor immune response with subsequent generation of immunologic memory. These findings support the potential for vaccine adjuvants to enhance the efficacy of in situ tumor vaccine approaches.
Visual cortex encodes timing information in humans and mice
Authors: Qingpeng Yu, Zedong Bi, Shize Jiang, Biao Yan, Heming Chen, Yiting Wang, Yizhan Miao, Kexin Li, Zixuan Wei, Yuanting Xie, Xinrong Tan, Xiaodi Liu, Hang Fu, Liyuan Cui, Lu Xing, Shijun Weng, Xin Wang, Yuanzhi Yuan, Changsong Zhou, Gang Wang, Liang Li, Lan Ma, Ying Mao, Liang Chen, Jiayi Zhang
Journal: Neuron (2022)
Population structure discovery in meta-analyzed microbial communities and inflammatory bowel disease using MMUPHin
Authors: Siyuan Ma, Dmitry Shungin, Himel Mallick, Melanie Schirmer, Long H. Nguyen, Raivo Kolde, Eric Franzosa, Hera Vlamakis, Ramnik Xavier, Curtis Huttenhower
Journal: Genome biology (2022)

Microbiome studies of inflammatory bowel diseases (IBD) have achieved a scale for meta-analysis of dysbioses among populations. To enable microbial community meta-analyses generally, we develop MMUPHin for normalization, statistical meta-analysis, and population structure discovery using microbial taxonomic and functional profiles. Applying it to ten IBD cohorts, we identify consistent associations, including novel taxa such as Acinetobacter and Turicibacter, and additional exposure and interaction effects. A single gradient of dysbiosis severity is favored over discrete types to summarize IBD microbiome population structure. These results provide a benchmark for characterization of IBD and a framework for meta-analysis of any microbial communities.
Social media content contributed to teenager’s death “in more than a minimal way,” says coroner
Authors: Clare Dyer
Journal: BMJ (2022)

The metaverse and non-fungible tokens (NFTs) were some of the hottest tech terms in 2021, according to a Google Trends search. Our review aims to describe the metaverse and NFTs in the context of their potential application in the treatment of mental health disorders. Advancements in technology have been changing human lives at an ever-increasing pace. Metaverse, also known as the three-dimensional (3D) internet, is the convergence of virtual reality (VR) and physical reality in a digital space. It could potentially change the internet as we know it, with NFTs as the key building blocks in the new expansive virtual ecosystem. This immersive 3D virtual world boasts the features of the real world with the added ability to change the surrounding environment according to individual needs and requirements. VR, augmented reality (AR) and mixed reality (MR) have been employed as tools in the treatment of various mental health disorders for the past decade. Studies have reported positive results on their effectiveness in the diagnosis and treatment of mental health disorders. VR/AR/MR have been hailed as a solution to the acute shortage of mental health professionals and the lack of access to mental healthcare. But, on the flip side, young adults tend to spend a significant amount of time playing 3D immersive games and using social media, which can lead to insecurity, anxiety, depression, and behavioural addiction. Additionally, endless scrolling through social media platforms negatively affects individuals9 attention span as well as aggravating the symptoms of adolescents with attention deficit hyperactivity disorder. We aimed to explore the ramifications of expanding applications of the metaverse on mental health. So far, no other review has explored the future of mental health in the context of the metaverse.
NOX1 is essential for TNFα-induced intestinal epithelial ROS secretion and inhibits M cell signatures
Authors: Nai-Yun Hsu, Shikha Nayar, Kyle Gettler, Sayali Talware, Mamta Giri, Isaac Alter, Carmen Argmann, Ksenija Sabic, Tin Htwe Thin, Huai-Bin Mabel Ko, Robert Werner, Christopher Tastad, Thaddeus Stappenbeck, Aline Azabdaftari, Holm H Uhlig, Ling-Shiang Chuang, Judy H Cho
Journal: Gut (2022)

Objective Loss-of-function mutations in genes generating reactive oxygen species (ROS), such as NOX1 , are associated with IBD. Mechanisms whereby loss of ROS drive IBD are incompletely defined. Design ROS measurements and single-cell transcriptomics were performed on colonoids stratified by NOX1 genotype and TNFα stimulation. Clustering of epithelial cells from human UC (inflamed and uninflamed) scRNASeq was performed. Validation of M cell induction was performed by immunohistochemistry using UEA1 (ulex europaeus agglutin-1 lectin) and in vivo with DSS injury. Results TNFα induces ROS production more in NOX1-WT versus NOX1-deficient murine colonoids under a range of Wnt-mediated and Notch-mediated conditions. scRNASeq from inflamed and uninflamed human colitis versus TNFα stimulated, in vitro colonoids defines substantially shared, induced transcription factors; NOX1-deficient colonoids express substantially lower levels of STAT3 (signal transducer and activator of transcription 3), CEBPD (CCAAT enhancer-binding protein delta), DNMT1 (DNA methyltransferase) and HIF1A (hypoxia-inducible factor) baseline. Subclustering unexpectedly showed marked TNFα-mediated induction of M cells (sentinel cells overlying lymphoid aggregates) in NOX1-deficient colonoids. M cell induction by UEA1 staining is rescued with H 2 O 2 and paraquat, defining extra- and intracellular ROS roles in maintenance of LGR5+ stem cells. DSS injury demonstrated GP2 (glycoprotein-2), basal lymphoplasmacytosis and UEA1 induction in NOX1-deficiency. Principal components analyses of M cell genes and decreased DNMT1 RNA velocity correlate with UC inflammation. Conclusions NOX1 deficiency plus TNFα stimulation contribute to colitis through dysregulation of the stem cell niche and altered cell differentiation, enhancing basal lymphoplasmacytosis. Our findings prioritise ROS modulation for future therapies.
Blockades of effector T cell senescence and exhaustion synergistically enhance antitumor immunity and immunotherapy
Authors: Xia Liu, Fusheng Si, David Bagley, Feiya Ma, Yuanqin Zhang, Yan Tao, Emily Shaw, Guangyong Peng
Journal: Journal for ImmunoTherapy of Cancer (2022)

Background Current immunotherapies still have limited successful rates among cancers. It is now recognized that T cell functional state in the tumor microenvironment (TME) is a key determinant for effective antitumor immunity and immunotherapy. In addition to exhaustion, cellular senescence in tumor-infiltrating T cells (TILs) has recently been identified as an important T cell dysfunctional state induced by various malignant tumors. Therefore, a better understanding of the molecular mechanism responsible for T cell senescence in the TME and development of novel strategies to prevent effector T cell senescence are urgently needed for cancer immunotherapy. Methods Senescent T cell populations in the TMEs in mouse lung cancer, breast cancer, and melanoma tumor models were evaluated. Furthermore, T cell senescence induced by mouse tumor and regulatory T (Treg) cells in vitro was determined with multiple markers and assays, including real-time PCR, flow cytometry, and histochemistry staining. Loss-of-function strategies with pharmacological inhibitors and the knockout mouse model were used to identify the potential molecules and pathways involved in T cell senescence. In addition, melanoma mouse tumor immunotherapy models were performed to explore the synergistical efficacy of antitumor immunity via prevention of tumor-specific T cell senescence combined with anti-programmed death-ligand 1 (anti-PD-L1) checkpoint blockade therapy. Results We report that both mouse malignant tumor cells and Treg cells can induce responder T cell senescence, similar as shown in human Treg and tumor cells. Accumulated senescent T cells also exist in the TME in tumor models of lung cancer, breast cancer and melanoma. Induction of ataxia-telangiectasia mutated protein (ATM)-associated DNA damage is the cause for T cell senescence induced by both mouse tumor cells and Treg cells, which is also regulated by mitogen-activated protein kinase (MAPK) signaling. Furthermore, blockages of ATM-associated DNA damage and/or MAPK signaling pathways in T cells can prevent T cell senescence mediated by tumor cells and Treg cells in vitro and enhance antitumor immunity and immunotherapy in vivo in adoptive transfer T cell therapy melanoma models. Importantly, prevention of tumor-specific T cell senescence via ATM and/or MAPK signaling inhibition combined with anti-PD-L1 checkpoint blockade can synergistically enhance antitumor immunity and immunotherapy in vivo. Conclusions These studies prove the novel concept that targeting both effector T cell senescence and exhaustion is an effective strategy and can synergistically enhance cancer immunotherapy.
Coagulopathy Associated With the Use of Moxalactam
Authors: Robert L. Pakter
Journal: JAMA (1982)

MOXALACTAM disodium (Moxam) is a new β-lactam antibiotic with a broad clinical spectrum and is considered by some a third-generation cephalosporin. This report documents the development of significant coagulopathy in two patients shortly after the administration of the drug. <h3>Report of Cases</h3><h3>Case 1.—</h3> A 68-year-old woman was admitted with left lower quadrant abdominal pain of two days' duration. After examination the patient underwent exploratory laparotomy and was found to have a gangrenous appendix with perforation.<i>Bacteroides fragilis</i>and group D streptococcus were cultured from the abdominal wound. Preoperative medications included methyldopa and hydrochlorothiazide. In the immediate postoperative period the patient was treated with moxalactam disodium, 2 g intravenously (IV) every eight hours; cimetidine, 300 mg IV every eight hours; and penicillin G potassium, 2 million units IV every four hours. The postoperative course was complicated by oliguria and serum creatinine elevation to 2.1 mg/dL on postoperative day 5, with
Effects of War on the Health Care of Bosnian Children
Authors: L. C. Miller, N. Langhans, J. G. Schaller, E. Zecevic
Journal: JAMA (1996)

<h3>To the Editor.</h3> —During the nearly 4 years that Sarajevo, the capital city of Bosnia-Herzegovina, was under siege, 1602 children were killed and 14952 were injured,<sup>1</sup>and 37% of the population became refugees.<sup>2</sup>The city was isolated from the world community and experienced extended periods without food, running water, electricity, or natural gas. The Sarajevo Pedijatrijska Klinika, the main children's hospital for the city and a tertiary referral center for Bosnia, was directly shelled and completely destroyed.<sup>3</sup>This disruption continues to affect the health care of Bosnian children even after the Dayton peace accord brought an end to fighting in the area.<sup>2</sup> We interviewed the families of all 60 children (mean age 4.1, median 2.9, 1 day to 14.5 years; 35 boys, 25 girls) admitted during February 1996 to the relocated Klinika. Information obtained included age, sex, anthropometric measurements, diagnoses, injuries sustained by the children and
Suppression of Gross Leukemia Cell-Surface Antigens: A Kind of Antigenic Modulation&lt;xref ref-type="fn" rid="FN1"&gt;2&lt;/xref&gt;
Authors: Tadao Aoki, Patricia A. Johnson
Journal: JNCI Journal of the National Cancer Institute (1972)

When Passage A Gross virus-induced C57BL/6 leukemia E♂G2 was transplanted into C57BL/6 mice immunized with AKR spontaneous leukemia K36, the group of cell-surface antigens GCSAa disappeared or diminished independently of GCSAb, G1X, and H-2b antigens. After transplantation of E♂G2 back into untreated C57BL/6 mice, GSCA reappeared to their original levels. Therefore, the disappearance of GCSAa indicates antigenic suppression. Although there are some differences between GCSA antigenic suppression and TL (thymus leukemia) antigenic modulation, the Former also can be categorized in a broad sense as a kind of antigenic modulation. Antibody to GCSA did not influence the budding of murine leukemia virus (Gross) from these E♂G2 cells.
Cellular Oxygen Metabolism During Sepsis and Shock
Authors: Eric C. Rackow
Journal: JAMA (1988)

SEPTIC (bacterial) shock usually develops as a complication of overwhelming infection.<sup>1</sup>The majority of cases are secondary to gram-negative aerobic bacilli; however, gram-positive organisms account for a smaller but significant proportion of cases. Shock develops in 25% to 50% of patients with gram-negative bacteremia.<i>Escherichia coli</i>remains the predominant pathogen in most series of septic shock, followed by the<i>Klebsiella</i>group and<i>Pseudomonas</i>species. Both the<i>Staphylococcus</i>and<i>Streptococcus</i>species account for most of the gram-positive infections. The genitourinary tract is the most common site of infection, with the gastrointestinal and respiratory tracts as the next most frequent sources of sepsis. Other common foci include the skin and wounds, the central nervous system, and infected intravenous catheters. Sepsis is not usually complicated by shock in persons younger than 40 years of age, except in young women during pregnancy, infants during the neonatal period, and patients with impairment of host
The Swiss heroin trials
Authors: G R Venning, A. Wodak, W. Hall, M. Farrell
Journal: BMJ (1998)

Further studies of heroin treatment are neededEditor-On the basis of a trial in Switzerland, 1 Farrell and Hall conclude that medically prescribed heroin is likely to have only a limited role in the future. 2 It is hard to know how any judgment can be made about this approach after only one randomised control trial, 3 one case-control study, 4 and the large but uncontrolled study that the authors commented on. 1 Farrell and Hall are right to emphasise the difficulty of disentangling the contribution of comprehensive social and psychological inventions in the impressive results obtained in this population. 1After more than three decades of research evaluating the effectiveness of methadone maintenance treatment it is safe to conclude that such interventions improve outcomes but difficult to be much more precise than this.Social and psychological interventions probably improve results of virtually all interactions between patients and the healthcare system.The authors say that the proposal to conduct a heroin trial in Australia damaged support for harm reduction.This is arguable.The mood in Australia has generally been more conservative over the past two years.The controversy over the heroin trial in Australia probably contributed to major improvements in a local methadone programme and certainly led directly to a commitment and funding for research on an expanded range of pharmacological treatments for heroin dependence.The authors question whether Australia is in the middle of a national heroin crisis.If a sixfold increase in mortality from drug overdose during the past 16 years 5 is not a crisis it is hard to know what would be.The Swiss heroin trial may have been more expensive than routine prescription methadone.But trials of new treatment are invariably more costly than providing well established treatments as a routine.Heroin
Prematurity and Risk of Childhood Cancer
Journal: JNCI Journal of the National Cancer Institute (1986)

Prematurity and Risk of Childhood Cancer Get access Christine Cole Johnson, Ph.D., Christine Cole Johnson, Ph.D. Department of Cancer Prevention University of Texas M.D. Anderson Hospital and Tumor Institute Houston, TX 77030 Search for other works by this author on: Oxford Academic PubMed Google Scholar Margaret R. Spitz, M.D.,M.P.H. Margaret R. Spitz, M.D.,M.P.H. Department of Cancer Prevention University of Texas M.D. Anderson Hospital and Tumor Institute Houston, TX 77030 Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 76, Issue 2, February 1986, Page 359, https://doi.org/10.1093/jnci/76.2.359 Published: 01 February 1986
Blood Platelet Monoamine Oxidase Activity in Psychiatric Patients
Authors: Eitan Friedman, Baron Shopsin, Gregory Sathananthan, Samuel Gershon
Journal: American Journal of Psychiatry (1974)

The authors measured monoamine oxidase (MAO) activity in blood platelets of normal control subjects, patients with schizophrenia, and patients with other psychiatric diagnoses. No differences were found among the groups as a whole. However, in the control group, women had significantly higher enzyme activity than men. Female schizophrenic patients showed a trend toward lower activity than did female control subjects, but did not differ from the male schizophrenic patients. The authors suggest that platelet MAO activity may be related to hormonal, dietary, or genetic factors but not to psychiatric diagnosis.
Association Between HTLV-III/ LAV Infection and Tuberculosis in Zaire
Authors: Jonathan Mann
Journal: JAMA (1986)

<h3>To the Editor.—</h3> Immunosuppression caused by drugs, infections, cancer, or other conditions is known to increase the risk of tuberculosis.<sup>1</sup>Studies of patients with the acquired immunodeficiency syndrome (AIDS)<sup>2,3</sup>and of the incidence of tuberculosis in young men in selected US cities<sup>4</sup>suggest that an increased risk of overt disease among persons previously infected with the tubercle bacillus may be associated with human T-cell lymphotropic virus type III/lymphadenopathy-associated virus (HTLV-III/LAV) infection. Project SIDA is a collaborative AIDS research project in Zaire, involving the Zairian Department of Public Health, the Public Health Service, and the Institute of Tropical Medicine, Antwerp, Belgium. In March 1985, project researchers determined the prevalence of antibody to HTLV-III/LAV in 231 (84%) of the 274 inpatients of the tuberculosis sanatorium in Kinshasa, Zaire. Of the 231 study participants, 159 (69% ) had confirmed pulmonary tuberculosis (positive results of sputum examination for acid-fast bacilli). Of these